The invention relates to a pharmaceutical preparation.
The term vitamin A stands for a number of chemically similar compounds with different effect in the human and animal organism. These include as essential groups the alcohol of the vitamin, retinol, the transport form of the vitamin in blood, the aldehyde, the biologically active metabolite in the visual process, retinal ester, the storage form of the vitamin in the liver and in mucous membranes and reproductive glands, and retinoic acid with various derivatives which play a part in particular in the differentiation processes of the skin. The vitamin is essential to man, i.e. a vitamin deficiency results if it is not taken in with food. The vitamin A deficiency manifests itself, depending on the duration of deprivation in hornification of the mucous membranes (Biesalski, H. K. Stofft, E., Wellner U., Niederauer, U., and Bassler, K. H. Vitamin A and ciliated cells. I. Respiratory epithelia, "Z. F. Ernahrungswissenschaft: 25, 114-122 (1986), and McDowell E. M., Keenan K. P., Huang M.: Effect of Vitamin A deprivation on Hamster, Brachial Epithelium, Virchow's Arch. (Cell. Pathol.), 45: 197-219, 1984 and McDowell E. M., Keenan K. P., Huang M.; Restoration of mucociliary Brachial Epithelium following Deprivation of Vitamin A, Virchow's Arch. (Cell. Pathol.) 45: 221-240, 184), in particular of the respiratory system, increased susceptibility to infections and with pronounced defect in the classic symptoms of keratinization of the conjunctiva of the eye up to complete destruction and blindness.
On intake of the vitamin most of the deficiency-enhanced alterations are reversible, in particular in the area of the mucous membranes. These typical changes induced by the vitamin A deficiency are found in similar manner in diseases of the mucous membranes of the respiratory system as caused by acute and chronic bronchitis, nicotine inhalation and also early cancerous changes. It has been possible to show in experimental investigations on animals and on humans that such changes not induced by vitamin A deficiency could be made reversible by systemic intake of the vitamin, usually in high doses. In particular in various forms of cancer the use of large-dose systemic vitamin A therapy is described with varying success in the sense of preventing recidivation after primary treatment of the tumor.
In systemic administration, to obtain a regression of the squamous metaplasia or to prevent renewed occurrence of such changes high concentrations must be used which in some cases lead to substantial side effects (cerebral pressure symptoms, liver cell metabolism disturbances, and others). In addition, there is a pronounced teratogenic effect in the first three-month period which forbids use of large-dose therapy in pregnancy (Bauernfeind JC. (1980): The safe use of vitamin A, The nutrition foundation, Washington D.C.).
Furthermore, an intake of vitamin A is also inadmissible in physiological concentration in the presence of disturbances of liver cell metabolism such as inflammation or cirrhosis because due to the simultaneously disturbed protein synthesis (lack of formation of the transport protein--RBP=retinol-binding protein) of the liver removal of the vitamin from the stores into which it is transferred after absorption is not possible and consequently further damage to the liver would arise (Smith, F. R. and Goodman, D. S. The effect of diseases of the liver, thyroid, and kidneys on the transport of vitamin A in human plasma. J. Clin. Invest.: 50, 2426 (1971); Weber, F. L., Mitchell, G. E., Powell, D. B., Reiser, B. J. and Banwell, J. G., Reversible hepatoxicity associated with hepatic vitamin A accumulation in a protein deficient patient. Gastroenterology: 82, 118-123 (1982)). In addition, the vitamin can only be taken up by the peripheral target tissue, such as the respiratory epithelium, and carry out its function when it is bound to precisely this transport protein.
An object of the present invention is therefore to avoid these disadvantages, in particular to permit an action of the vitamin A or similar compounds on the mucous membranes of the urogenital tract, intestinal tract and the respiratory epithelium, the epithelia of the nose-throat cavity and preferably the epithelia of the tracheal and deep bronchial tract.